Apolipoprotein D (“ApoD”) is a 169 residue, 29 kDa glycoprotein member of the lipocalcin family that binds to several ligands, including progesterone and arachidonic acid, and is associated with HDL in plasma. It is highly expressed in nervous tissue (e.g., brain in glia and neurons) and apparently at lower levels in many other tissues under normal conditions. ApoD expression increases with aging and in neurological and psychiatric disorders (e.g., Alzheimer's Disease, Parkinson's Disease, Schizophrenia, bipolar disorder, and by the antipsychotic clozapine, and in some cancers). While ApoD has been widely used as a disease marker, little is known about its potential therapeutic effects.
Tissue damage can result from an imbalance between oxygen supply and demand in tissue, i.e., ischemia. For instance, myocardial ischemia is a pathological state associated with coronary artery disease that results from reduced blood perfusion in the heart, leading to impaired oxygen supply to the heart. Current interventions for improving blood flow to damaged heart tissue are mostly invasive, including stent placement, coronary bypass surgery, angioplasty, and endarterectomy. The high risk associated with these invasive procedures underscores the need for additional therapies and therapeutic agents for treating or reducing tissue damage resulting from ischemia, for example, myocardial ischemia.